Disease Profile

Isolated congenital megalocornea

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of Onset

-

ICD-10

Q15.8

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

Congenital anterior megalophthalmia; Megalocornea; MGC1;

Categories

Congenital and Genetic Diseases; Eye diseases

Summary

Isolated congenital megalocornea affects the cornea, the part of the eye that lets in light. The symptoms of isolated congenital megalocornea include mild nearsightedness, light sensitivity, and/or unusual vibration of the iris. At birth, the corneas are thin and enlarged. Cataracts may develop by 30-50 years of age. Other complications may include other cornea abnormalities, lens dislocation, and break down of the iris. Isolated congenital megalocornea occurs when the CHRDL1 gene is not working correctly. It is inherited in an X-linked recessive pattern. Diagnosis is made through a clinical examination and confirmed by DNA testing. Treatment is based on managing the symptoms and should include regular monitoring of eye health.[1][2][3][4]

Symptoms

The following list includes the most common signs and symptoms in people with isolated congenital megalocornea. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms of isolated congenital megalocornea may include:

At birth, the cornea is enlarged and thinner than normal. The pressure in the eye is normal. The cornea may start to breakdown, or it may develop some cloudiness. Other changes include lens dislocation and break down of the lens. Visual problems include blurriness, glare, flashes, and floaters.[1][2][5]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Retinal detachment
Detached retina
0000541
1%-4% of people have these symptoms
Corneal arcus
0001084
Iris transillumination defect
0012805
Megalocornea
Enlarged cornea
0000485
Reduced visual acuity
Decreased clarity of vision
0007663
Percent of people who have these symptoms is not available through HPO
Astigmatism
Abnormal curving of the cornea or lens of the eye
0000483
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Decreased corneal thickness
Thin cornea
0100689
Deep anterior chamber
0007765
Glaucoma
0000501
Iridodonesis
0100693
Lens subluxation
Partially dislocated lens
0001132
Miosis
Constricted pupils
Pupillary constriction

[ more ]

0000616
Mosaic corneal dystrophy
0007836
X-linked recessive inheritance
0001419

Cause

Isolated congenital megalocornea occurs when the CHRDL1 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1]

Diagnosis

Isolated congenital megalocornea is diagnosed based on a clinical examination looking for the presence of characteristic symptoms. Ultrasound can sometimes be used to help tell the difference between isolated congenital megalocornea and other conditions. Genetic testing may be used to confirm the diagnosis.[1][4]

Treatment

Treatment is aimed at managing the symptoms that are present. Glasses and contact lens may be used to correct vision impairment. Regular follow-up is needed to monitor for long-term complications like lens dislocation, cataracts, and glaucoma.[3]

Some of the specialists that might be involved in the care of someone with isolated congenital megalocornea include:

  • Ophthalmologist
  • Medical geneticist

Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

References

  1. Davidson E, Cheong SS, Hysi PG, et al. Association of CHRDL1 mutations and variants with X-linked megalocornea, Neuhäuser syndrome and central corneal thickness. PLoS One. 2014; 9(8):e104163. https://pubmed.ncbi.nlm.nih.gov/25093588.
  2. Webb TR, Matain M, Gardner JC, et al. X-linked megalocornea caused by mutations in CHRDL1 identifies an essential role for ventroptin in anterior segment development. Am J Hum Genet. 2012; 90(2):247-259. https://pubmed.ncbi.nlm.nih.gov/22284829.
  3. Pfirrmann T, Emmerich D, Ruokonen P, et al. Molecular mechanism of CHRDL1-mediated X-linked megalocornea in humans and in Xenopus model. Hum Mol Genet. 2015; 24(11):3119-3132. https://pubmed.ncbi.nlm.nih.gov/25712132.
  4. Han J, Young JW, Frausto RF, Isenberg SJ, Aldave AJ. X-linked Megalocornea Associated with the Novel CHRDL1 Gene Mutation p.(Pro56Leu*8). Ophthalmic Genet. 2015; 36(2):145-148. https://pubmed.ncbi.nlm.nih.gov/24073597.
  5. Moshirfar M, Hastings J, Ronquillo Y. Megalocornea. In: StatPearls. 2020; https://pubmed.ncbi.nlm.nih.gov/32119261.